Exogenous Allergic Alveolitis - Clinical Guidelines, General Information

2024 Author: Josephine Shorter | [email protected]. Last modified: 2024-01-07 17:49

Exogenous allergic alveolitis: etiology, pathogenesis, treatment

Exogenous allergic alveolitis is also called hypersensitivity pneumonitis. The abbreviation of the disease is EAA. This term reflects a whole group of diseases that affect the interstitium of the lungs, that is, the connective tissue of organs. The inflammation is concentrated in the pulmonary parenchyma and small airways. It occurs when a variety of antigens (fungi, bacteria, animal proteins, chemicals) enter them from the outside.

For the first time exogenous allergic alveolitis was described by J. Campbell in 1932. He identified it in 5 farmers who suffered from ARVI symptoms after working with hay. Moreover, this hay was wet and contained mold spores. Therefore, this form of the disease began to be called "farmer's lung."

In the future, it was possible to establish that allergic alveolitis of the exogenous type can be triggered by other reasons. In particular, in 1965, C. Reed and her colleagues, found similar symptoms in three patients who were breeding pigeons. They began to call this alveolitis "bird fancier's lung."

Statistics of recent years indicate that the disease is quite widespread among people who, due to their professional activities, interact with feathers and down of birds, as well as with mixed feed. Exogenous allergic alveolitis will be diagnosed in 42 out of 100,000 population. At the same time, it is impossible to predict exactly which person who is allergic to down or feathers will develop alveolitis.

As practice shows, from 5 to 15% of people who have interacted with high concentrations of allergens will develop pneumonitis. The prevalence of alveolitis among people who work with low concentrations of sensitizing substances is not known to date. However, this problem is quite acute, since the industry is developing more and more intensively every year, which means that more and more people are involved in such activities.

Content:

• Etiology
• Pathogenesis of exogenous allergic alveolitis
• Histological picture of EAA
• Symptoms of exogenous allergic alveolitis
• Diagnosis of exogenous allergic alveolitis
• Treatment of exogenous allergic alveolitis
• Forecast and prevention

Etiology

Allergic alveolitis develops due to inhalation of an allergen that enters the lungs along with the air. A variety of substances can act as an allergen. The most aggressive allergens in this regard are fungal spores from rotten hay, maple bark, sugar cane, etc.

Also, one should not write off plant pollen, protein compounds, house dust. Some medications, for example, antibiotics or nitrofuran derivatives, can cause allergic alveolitis even without previous inhalation, and after entering the body in other ways.

It is not only the fact that allergens enter the respiratory tract that matter, but also their concentration and size. If the particles do not exceed 5 microns, then it will not be difficult for them to reach the alveoli and provoke a hypersensitivity reaction in them.

Since the allergens that cause EAA are most often associated with the professional activity of a person, the types of alveolitis have been named for various professions:

• Farmer's lung. Antigens are found in moldy hay, among them: Thermophilic Actinomycetes, Aspergillus spp, Mycropolyspora faeni, Thermoactinomycas vulgaris.
• Bird lovers' lung. Allergens are found in feces and bird dandruff. These are the whey proteins of birds.
• Bagassosis. The allergen is sugarcane, namely Mycropolysporal faeni and Thermoactinomycas sacchari.
• Lung of mushroom growers. Compost becomes the source of allergens, while Mycropolysporal faeni and Thermoactinomycas vulgaris act as antigens.
• Lung of persons using air conditioners. Air humidifiers, heaters and air conditioners are the source of the spread of antigens. Sensitization is provoked by such pathogens as: Thermoactinomycas vulgaris, Thermoactinomycas viridis, Ameba, Fungi.
• Suberose. The bark of the cork tree becomes the source of allergens, and Penicillum frequentans acts as the allergen itself.
• The malt brewer's lung. The source of antigens is moldy barley, and the allergen itself is Aspergillus clavatus.

• Disease of cheese makers. The source of antigens is particles of cheese and mold, and the antigen itself is Penicillum cseii.
• Sequoise. Allergens are found in sequoia wood dust. They are represented by Graphium spp., Upullaria spp., Alternaria spp.
• Lung of detergent manufacturers. The allergen is found in enzymes and detergents. It is represented by Bacillus subtitus.
• Lung of laboratory assistants. The sources of allergens are dandruff and rodent urine, and the allergens themselves are represented by the proteins of their urine.
• Lung sniffing powder of the pituitary gland. The antigen is represented by pork and bovine proteins, which are found in the pituitary gland powder.
• Lung of those employed in the plastics industry. Diisocyanates become the source of sensitization. Allergens are: Toluene diisocianate, diphenylmethane diisocianate.
• Summer pneumonitis. The disease develops due to the ingestion of dust from wet living quarters into the respiratory tract. Pathology is common in Japan. Trichosporon cutaneum becomes the source of allergens.

Of the listed allergens, in terms of the development of exogenous allergic alveolitis, thermophilic actinomycetes and avian antigens are of particular importance. In areas with a high development of agriculture, it is actinomycetes that occupy a leading position in terms of the incidence of EAA. They are represented by bacteria that do not exceed 1 micron in size. A distinctive feature of such microorganisms is that they possess the properties of not only microbes, but also fungi. Many thermophilic actinomycetes are located in soil, compost, and water. They also live in air conditioners.

Such varieties of thermophilic actinomycetes as Mycropolyspora faeni, Thermoactinomycas vulgaris, Thermoactinomycas viridis, Thermoactinomycas sacchari, Thermoactinomycas scandidum lead to the development of exogenous allergic alveolitis.

All of these representatives of the flora pathogenic for humans begin to multiply actively at a temperature of 50-60 ° C. It is in such conditions that the processes of organic decay are started. A similar temperature is maintained in heating systems. Actinomycetes can provoke bagassosis (lung disease in people who work with sugarcane), cause a disease called "farmer's lung", "mushroom pickers (mushroom growers) lung", etc. All of them are listed above.

The antigens that affect humans interacting with birds are serum proteins. These are albumin and gamma globulins. They are present in bird droppings, in secretions from the skin glands of pigeons, parrots, canaries, etc.

People who care for birds are exposed to alveolitis through prolonged and regular interaction with animals. Proteins of cattle, as well as pigs, can provoke the disease.

The most active fungal antigen is Aspergillus spp. Various types of this microorganism can cause suberosis, malt brewer's lung or cheese maker's lung.

It is in vain to believe that, living in the city and not doing agriculture, a person cannot get sick with exogenous allergic alveolitis. In fact, Aspergillus fumigatus thrives in damp rooms that are rarely ventilated. If the temperature in them is high, then the microorganisms begin to multiply rapidly.

Also at risk for the development of allergic alveolitis are people whose professional activities are associated with reactogenic chemical compounds, for example, with plastic, resins, paints, polyurethane. Phthalic anhydride and diisocyanate are considered especially dangerous.

Depending on the country, the following prevalence of different types of allergic alveolitis is traced:

• Budgerigar's lung is most commonly diagnosed in the UK.
• Lung for air conditioners and moisturizers in America.
• Summer type of alveolitis, caused by seasonal reproduction of fungi of the Trichosporon cutaneun species, is diagnosed in 75% of cases in Japanese.
• In Moscow and in cities with large industrial enterprises, patients with a reaction to avian and fungal antigens are most often identified.

Pathogenesis of exogenous allergic alveolitis

The human respiratory system is regularly exposed to dust particles. Moreover, this applies to both organic and inorganic contaminants. It has been established that antigens of one type can cause the development of various pathologies. Some people develop bronchial asthma, while others develop chronic rhinitis. There are also people who have allergic dermatosis, that is, skin lesions. We must not forget about allergic conjunctivitis. Naturally, exogenous alveolitis is not the last in the list of the listed pathologies. What kind of disease will develop in a particular person depends on the strength of the effect, on the type of allergen, the state of the body's immune system and other factors.

In order for a patient to manifest exogenous allergic alveolitis, a combination of several factors is necessary:

• Sufficient dose of airborne allergens.
• Their long-term effect on the respiratory system.
• Defined size of pathological particles, which is 5 microns. Less commonly, the disease develops when large antigens enter the respiratory system. In this case, they should settle in the proximal bronchi.

The overwhelming majority of people who are faced with such allergens do not suffer from EAA. Therefore, scientists believe that several factors should act simultaneously on the human body. They have not been studied enough, but there is an assumption that genetics and the state of immunity matter.

Exogenous allergic alveolitis is rightfully referred to as immunopathological diseases, the undoubted cause of the development of which are allergic reactions of types 3 and 4. Also, non-immune inflammation should not be ignored.

The third type of immunological reaction is of particular importance at the initial stages of the development of pathology. The formation of immune complexes occurs directly in the interstitium of the lungs when the pathological antigen interacts with antibodies of the IgG class. The formation of immune complexes leads to damage to the alveoli and interstitium, increasing the permeability of the vessels feeding them.

The formed immune complexes make the complement system and alveolar macrophages activate. As a result, there is a release of toxic and anti-inflammatory products, hydrolytic enzymes, cytokines (tumor necrosis factor - TNF-a and interleukin-1). All this causes an inflammatory response at the local level.

Subsequently, the cells and matrix components of the interstitium begin to die off, and the inflammation becomes more intense. Monocytes and lymphocytes are supplied to the site of injury in significant quantities. They ensure the maintenance of the delayed-type hypersensitivity reaction.

Facts that confirm that with exogenous allergic alveolitis, immunocomplex reactions are important:

• After interaction with the antigen, inflammation develops rapidly, within 4-8 hours.
• In washings of exudate from the bronchi and alveoli, as well as in the serum of the blood, high concentrations of IgG antibodies are found.
• In the lung tissue taken for histology, immunoglobulin, complement components and the antigens themselves are found in patients with an acute form of the disease. All of these substances are immune complexes.
• When performing skin tests using highly purified antigens, pathological for a particular patient, a classic Arthus-type reaction develops.
• After performing provocative tests with inhalation of pathogens, the number of neutrophils in the bronchoalveolar lavage fluid increases in patients.

Type 4 immune responses include CD + T cell delayed hypersensitivity and CD8 + T cell cytotoxicity. After the antigens enter the respiratory system, delayed-type reactions develop in 1-2 days. Damage to immune complexes leads to the release of cytokines. They, in turn, cause leukocytes and the endothelium of the lung tissue to express adhesive molecules on the surface. Monocytes and other lymphocytes react to them, which actively arrive at the site of the inflammatory reaction.

At the same time, interferon gamma activates macrophages that produce CD4 + lymphocytes. This is the hallmark of a delayed-type reaction that, thanks to macrophages, lasts for a long time. As a result, the patient forms granulomas, collagen begins to be secreted in excess amounts (fibroblasts are activated by growth cells), and interstitial fibrosis develops.

Facts that confirm that with exogenous allergic alveolitis, delayed immunological reactions of type 4 are important:

• T-lymphocytes are found in the blood memory. They are present in the lung tissue of patients.
• In patients with acute and subacute exogenous allergic alveolitis, granulomas, infiltrates with accumulation of lymphocytes and monocytes, as well as interstitial fibrosis are detected.
• Experiments on laboratory animals with EAA made it possible to establish that CD4 + T-lymphocytes are required for the induction of the disease.

Histological picture of EAA

In most cases, patients with exogenous allergic alveolitis are found to have granulomas without curdled plaque. They are detected in 79-90% of patients.

In order not to confuse the granulomas that develop with EAA and with sarcoidosis, you need to pay attention to the following differences:

• With EAA, the granulomas are smaller.
• Granulomas have no clear boundaries.
• There are more lymphocytes in granulomas.
• Alveolar walls in EAA are thickened, they have lymphocytic infiltrates.

After contact with the antigen is excluded, the granulomas disappear on their own within six months.

With exogenous allergic alveolitis, the inflammatory process is caused by lymphocytes, monocytes, macrophages and plasma cells. Foamy alveolar macrophages accumulate within the alveoli themselves, and lymphocytes in the interstitium. When the disease has just begun to develop, patients have a protein and fibrinous effusion that is located inside the alveoli. Also, patients are diagnosed with bronchiolitis, lymphatic follicles, peribronchial inflammatory infiltrates, which are concentrated in the small airways.

So, the disease is characterized by a triad of morphological changes:

• Alveolitis.
• Granulomatosis.
• Bronchiolitis.

Although sometimes one of the signs may drop out. Rarely, with exogenous allergic alveolitis, patients develop vasculitis. He was diagnosed in a patient posthumously, as indicated in the relevant documents. With pulmonary hypertension in patients, hypertrophy of the arteries and arterioles occurs.

The chronic course of EAA leads to fibrinous changes, which can be of varying intensity. However, they are characteristic not only for exogenous allergic alveolitis, but also for other chronic lung diseases. Therefore, it cannot be called a pathognomic sign. With long-term current alveolitis in patients, the pulmonary parenchyma undergoes pathological changes like the cellular lung.

Symptoms of exogenous allergic alveolitis

The disease develops most often in people who are not prone to allergic reactions. Pathology manifests itself after prolonged interaction with sources, the spread of antigens.

Exogenous allergic alveolitis can occur in 3 types:

Acute symptoms

The acute form of the disease occurs after a large amount of antigen enters the respiratory tract. This can happen both at home and at work or even outdoors.

After 4-12 hours, a person's body temperature rises to high levels, chills develop, and weakness increases. There is heaviness in the chest, the patient begins to cough, he is pursued by shortness of breath. There is aches in the joints and muscles. Sputum during coughing does not appear often. If it leaves, then there is little of it and it consists mainly of mucus.

Another symptom typical of acute EAA is headache that is concentrated in the forehead.

During the examination, the doctor notes cyanosis of the skin. When listening to the lungs, crepitations and wheezing are heard.

After 1-3 days, the symptoms of the disease disappear, but after another interaction with the allergen, they increase again. General weakness and lethargy, combined with shortness of breath, can bother a person for several weeks after the acute stage of the disease resolves.

The acute form of the disease is not often diagnosed. Therefore, doctors confuse it with SARS, provoked by viruses or mycoplasmas. Professionals should be wary of farmers and differentiate between EAA symptoms and pulmonary mycotoxicosis symptoms that develop when fungal spores enter lung tissue. In patients with myotoxicosis, X-ray of the lungs does not reveal any pathological changes, and the serum part of the blood does not have precipitating antibodies.

Subacute type symptoms

Symptoms of the subacute form of the disease are not as pronounced as in the acute form of alveolitis. Such alveolitis develops due to prolonged inhalation of antigens. Most often this happens at home. So, subacute inflammation in most cases is provoked by caring for poultry.

The main manifestations of subacute exogenous allergic alveolitis include:

• Shortness of breath that worsens after physical activity.
• Increased fatigue.
• A cough that produces clear mucus.
• At an early stage of the development of pathology, body temperature may increase.

Crepitations when listening to the lungs will be gentle.

It is important to distinguish subacute EAA from sarcoidosis and other pulmonary interstitial diseases.

Chronic symptoms

The chronic form of the disease develops in people who interact with low doses of antigens for a long time. In addition, subacute alveolitis can become chronic if not treated.

The chronic course of the disease is indicated by symptoms such as:

• Dyspnea worsening over time, which becomes evident with physical exertion.
• Severe weight loss, which can reach anorexia.

The disease threatens the development of cor pulmonale, interstitial fibrosis, heart and respiratory failure. Since chronic exogenous allergic alveolitis begins to develop latently and does not give pronounced symptoms, its diagnosis is difficult.

Diagnosis of exogenous allergic alveolitis

To identify the disease, it is necessary to rely on an X-ray examination of the lungs. Depending on the stage of development of alveolitis and its form, radiological signs will differ.

Acute and subacute form of the disease leads to a decrease in the transparency of the fields like ground glass and to the spread of nodular-mesh darkening. The nodules do not exceed 3 mm in size. They can be found all over the lungs.

The upper part of the lungs and their basal parts are not covered with nodules. If a person stops interacting with antigens, then after 1-1.5 months the radiological signs of the disease disappear.

If the disease has a chronic course, then the x-ray picture shows linear shadows with a clear outline, darkened areas represented by nodules, changes in the interstitium, and a decrease in the size of the pulmonary fields. When the pathology has a running course, the cellular lung is visualized.

CT is a method that is much more accurate than X-ray. The study reveals signs of EAA, which are invisible with standard radiography.

A blood test in patients with EAA is characterized by the following changes:

• Leukocytosis up to 12-15x10 ³ / ml. Less often, the level of leukocytes reaches 20-30x10 ³ / ml.
• Leukocyte formula shifts to the left.
• An increase in the level of eosinophils does not occur, or it may increase slightly.
• ESR in 31% of patients rises to 20 mm / h, and in 8% of patients to 40 mm / h. In other patients, ESR remains within normal limits.
• The level of lgM and lgG rises. Sometimes there is a jump in class A immunoglobulins.
• In some patients, the rheumatoid factor is activated.
• The level of total LDH rises. If this occurs, acute inflammation in the lung parenchyma can be suspected.

To confirm the diagnosis, Ouchterloni double diffusion, Ouchterloni micro-diffusion, counter immunoelectrophoresis and ELISA (ELISA, ELIEDA) methods are used. They allow you to identify specific precipitating antibodies to the antigens that caused the allergy.

In the acute phase of the disease, precipitating antibodies will circulate in the blood of almost every patient. When the allergen stops interacting with patients' lung tissue, antibody levels drop. However, they can be present in the serum part of the blood for a long time (up to 3 years).

When the disease is chronic, no antibodies are detected. There is also the possibility of getting false positive results. In farmers without alveolitis symptoms, they are detected in 9-22% of cases, and in birdwatchers in 51% of cases.

In patients with EAA, the values of precipitating antibodies have no relationship with the activity of the pathological process. A variety of factors can affect their level. So, for people who smoke, it will be underestimated. Therefore, the detection of specific antibodies cannot be considered proof of EAA. At the same time, their absence in the blood does not indicate that there is no disease. However, antibodies should not be disregarded, since if there are appropriate clinical signs, they can strengthen the existing assumption.

The test for a decrease in the diffuse capacity of the lungs is indicative, since other functional changes in EAA are characteristic of other types of pathologies accompanied by damage to the interstitium of the lungs. Hypoxemia in patients with allergic alveolitis is observed in a calm state, and intensifies with physical exertion. Violation of ventilation of the lungs occurs in a restrictive manner. Signs of airway hyperresponsiveness are diagnosed in 10-25% of patients.

Inhalation tests were first used to detect allergic alveolitis back in 1963. Aerosols were made from dust taken from moldy hay. They led to an exacerbation of the symptoms of the disease in patients. At the same time, the extracts taken from "pure hay" did not cause such a reaction in patients. In healthy individuals, even mildewed aerosols did not provoke pathological signs.

Provocative tests in patients with bronchial asthma do not cause the appearance of rapid immunological reactions, do not provoke disturbances in the functioning of the lungs. While in people with a positive immune response, they lead to changes in the functioning of the respiratory system, to an increase in body temperature, chills, weakness and dyspnea. After 10-12 hours, these manifestations go away on their own.

It is possible to confirm the diagnosis of EAA without performing provocative tests, therefore they are not used in modern medical practice. They are used only by experts who need to confirm the cause of the disease. Alternatively, it is sufficient to observe the patient in his usual conditions, for example, at work or at home, where there is contact with the allergen.

Bronchoalveolar lavage (BAL) allows you to assess the composition of the contents of the alveoli and distant parts of the lungs. The diagnosis can be confirmed by the detection in it of a fivefold increase in cellular elements, and 80% of them will be represented by lymphocytes (mainly T cells, namely CD8 + lymphocytes).

The immunoregulatory index in patients is reduced by less than one. With sarcoidosis, this figure is 4-5 units. However, if lavage was performed in the first 3 days after the acute development of alveolitis, then the number of neutrophils will be increased, and lymphocytosis is not observed.

In addition, lavage allows you to detect an increase in the number of mast cells dozens of times. This concentration of mast cells can persist for up to 3 months or more after contact with an allergen. This indicator characterizes the activity of the fibrin production process. If the disease has a subacute course, then plasma cells will be found in the lavage.

Differential diagnosis

Diseases from which exogenous allergic alveolitis must be distinguished:

• Alveolar cancer or lung metastases. With cancerous tumors, there is no connection between the symptoms of the disease and contact with allergens. Pathology is constantly progressing, characterized by severe manifestations. In the serum part of the blood, precipitating antibodies to allergens are not released. Information can also be clarified using lung radiography.
• Miliary tuberculosis. In this disease, there is also no relationship with allergens. The infection itself has a severe course and long-term development. Serological methods allow detecting antibodies for tuberculosis antigen, while they do not appear for exoallergens. Do not forget about X-ray examination.
• Sarcoidosis This disease is not associated with a person's professional activities. With it, not only the respiratory system suffers, but also other body systems. The hilar lymph nodes in the chest are inflamed on both sides, there is a weak or negative reaction to tuberculin. Kveim's reaction, on the other hand, will be positive. Sarcoidosis can be confirmed with histological examination.
• Other fibrosing alveolitis. With them, most often, patients develop vasculitis, and systemic damage to the connective tissue affects not only the lungs, but also the body as a whole. If the diagnosis is doubtful, a lung biopsy is performed with further histological examination of the material obtained.
• Pneumonia. This disease develops after suffering a cold. The x-ray shows darkening, which appears due to tissue infiltration.

ICD-10 classifies exogenous allergic alveolitis into class X "Diseases of the respiratory system."

Clarifications:

• J 55 Respiratory tract disease caused by specific dust.
• J 66.0 Byssinosis.
• J 66.1 Disease of flax rappers.
• J 66.2 Cannabiosis.
• J 66.8 Respiratory tract disease due to other specified organic dusts.
• J 67 Hypersensitive pneumonitis.
• J 67.0 Farmer's (agricultural worker's) lung.
• J 67.1 Bagassosis (from sugar cane dust)
• J 67.2 Poultry farmer lung.
• J 67.3 Suberose
• J 67.4 Malt Lung.
• J 67.5 Lung of the mushroom worker.
• J 67.6 Maple bark picker's lung.
• J 67.8 Hypersensitive pneumonitis due to other organic dust.
• J 67.9 Hypersensitive pneumonitis due to other unspecified organic dust.

The diagnosis can be formulated as follows:

• Exogenous allergic alveolitis (farmer's lung), acute form.
• Drug-induced allergic alveolitis caused by furazolidone, subacute form, with respiratory failure.
• Exogenous allergic alveolitis (lung of poultry farmers), chronic form. Chronic lung heart, chronic bronchitis.

Treatment of exogenous allergic alveolitis

To cope with the disease, it is necessary to completely eliminate the interaction of the patient and the allergen. A person during work must use masks, special filters. It is highly desirable to change your job and your habits. In order to prevent the progression of pathology, it is important to identify it at the early stages of development. If contact with the allergen continues, the changes in the lungs will become irreversible.

A severe course of alveolitis requires the appointment of glucocorticosteroids. The dosage for patients with the acute phase of the disease is 0.5 mg per 1 kg of body weight (for Prednisolone). Duration of treatment: 14-28 days. Then the dose of the drug is gradually reduced.

For subacute and chronic course of the disease, Prednisolone is prescribed at a dosage of 1 mg / kg. The course lasts 1-2 months. Then the dose is reduced to 5-10 mg per day. Cancellation of the drug is carried out after the symptoms of the pathology recede, or if it does not bring the desired effect. If, during a decrease in the dose of Prednisolone, the patient's well-being worsens again, then it is increased.

Ingacort is an inhaled corticosteroid. The drug has been widely used for the treatment of exogenous allergic alveolitis in recent years. The patient is prescribed 2 breaths 2 times per day. The maximum daily dose is 1000 mcg.

If the disease persists with the use of corticosteroid drugs, D-penicillamine may be prescribed. Although there is no scientific confirmation of such therapy.

Patients with pulmonary hyperreactivity are prescribed inhaled bronchodilators. If the disease has led to the development of complications, then antibiotics, diuretics, oxygen, etc. are used.

Forecast and prevention

To prevent the development of the disease, you need to minimize all kinds of contact with allergens. So, hay should be thoroughly dried, silo pits should be open. Premises in production must be thoroughly ventilated, and when animals and birds are in them, sanitary and hygienic requirements must be strictly observed. Air conditioners and ventilation systems must be processed efficiently and on time, etc.

If the alveolitis has already developed, then the patient should exclude contact with allergens. When professional activity becomes the culprit, the job is changed.

The forecast is different. If the disease was diagnosed in the early stages, then the pathology can resolve on its own. Relapses of alveolitis lead to the fact that the lung tissue undergoes irreversible changes. This worsens the prognosis, as well as complications of alveolitis or its chronic course.

Author of the article: Alekseeva Maria Yurievna | Therapist

Education: From 2010 to 2016 Practitioner of the therapeutic hospital of the central medical-sanitary unit No. 21, city of elektrostal. Since 2016 she has been working in the diagnostic center No. 3.